In 1984, Borghi et al. reported that obese non-diabetic insulin-resistant and obese glucose-intolerant subjects already exhibited impaired oral glucose-induced glucagon suppression, even in presence of endogenous hyperinsulinemia and hypothesized that alpha-cells might be resistant to the insulin’s suppressive effect on glucagon secretion [31]. The gene discussed is GCG; the disease is hyperinsulinism.